ArticleJCI insight2024
Anti-CELA1 antibody KF4 prevents emphysema by inhibiting stretch-mediated remodeling.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Microcystin-LR-Induced Oxidative Stress, Transcriptome Changes, Intestinal Microbiota, and Histopathology inAnimals : an open access journal from MDPI · 2026Article
- Novel murine partial tracheal occlusion model with altered respiratory dynamics.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Targeting CELA1 to Improve Septation in the Mouse Hyperoxia Model of Impaired Alveolar Development.American journal of respiratory cell and molecular biology · 2025Article
- KF4 Anti-Chymotrypsin-like Elastase 1 Antibody and Purified Alpha-1 Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- KF4 anti-CELA1 Antibody and Purified α1-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine α1-Antitrypsin Deficiency.bioRxiv : the preprint server for biology · 2024Article
- Cloning, bioinformatics analysis and expression of the cysteine dioxygenase type 1 (CDO1) gene in domestic yak.Frontiers in veterinary science · 2024Article
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Authors and funding
16 authors at 10 institutions in 2 countries.
Funding
Abstract
There are no therapies to prevent emphysema progression. Chymotrypsin-like elastase 1 (CELA1) is a serine protease that binds and cleaves lung elastin in a stretch-dependent manner and is required for emphysema in a murine antisense oligonucleotide model of α-1 antitrypsin (AAT) deficiency. This study tested whether CELA1 is important in strain-mediated lung matrix destruction in non-AAT-deficient emphysema and the efficacy of CELA1 neutralization. Airspace simplification was quantified after administration of tracheal porcine pancreatic elastase (PPE), after 8 months of cigarette smoke (CS) exposure, and in aging. In all 3 models, Cela1-/- mice had less emphysema and preserved lung elastin despite increased lung immune cells. A CELA1-neutralizing antibody was developed (KF4), and it inhibited stretch-inducible lung elastase in ex vivo mouse and human lung and immunoprecipitated CELA1 from human lung. In mice, systemically administered KF4 penetrated lung tissue in a dose-dependent manner and 5 mg/kg weekly prevented emphysema in the PPE model with both pre- and postinjury initiation and in the CS model. KF4 did not increase lung immune cells. CELA1-mediated lung matrix remodeling in response to strain is an important contributor to postnatal airspace simplification, and we believe that KF4 could be developed as a lung matrix-stabilizing therapy in emphysema.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.